AB0012 IDENTIFICATION OF NEW BIOMARKERS FOR SINOMENINE TREATMENT IN RHEUMATOID ARTHRITIS BASED ON BIOINFORMATICS ANALYSIS
Authors: X. Shen, L. Yanqun, X. Guo, W. Linfeng, J. Zhang, Z. Feng
Journal: Annals of the Rheumatic Diseases (2022)

Background Sinomenine (SIN) were extracted from Caulis Sinomenii and achieved an remarkable therapeutic effect for Rheumatoid Arthritis (RA). However, the mechanism of SIN acting on RA is not clear yet. Objectives To excavate potential targets and mechanisms of SIN for RA through bioinformatics. Methods The microarray data were downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was used to identify differentially expressed genes (DEGs) and the unique value was retained. The potential targets of active compounds from various databases were screened. Based on the overlapping genes, Cytoscape 3.7.2 software was used to construct a protein-protein interactions (PPI) network and to visualize the mechanisms of the treatment by Gene Ontology (GO) enrichment analysis Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis by DAVID database. Finally, we used AutoDockTools 1.5.6 for molecular docking. Results A total of 5053 DEGs and 1070 intersections were obtained, including 486 up-regulated and 584 down-regulated targets. 298 SIN targets were collected from various databases, 84 potential targets were obtained by intersecting with DEGs. There are 80 nodes and 305 edges were obtained in PPI network. Based on the degree, the top 10 target genes were AKT1, RGFR, MTOR, JAK2, NOS3, IL2, IL6, MMP9, MAPK8, HSP9OAA1. The core targets was most relevant to protein phosphorylation, signal transduction though GO analysis. The results of the KEGG enrichment analysis included PI3K-Akt signaling pathway and Neuroactive ligand-receptor interaction. Following analysis found that AKT1, EGFR, MTOR and JAK2 existed in the PI3K-Akt signaling pathway. Molecular docking was used to confirm that the binding energy of AKT1 was -7.68 kJ mol -1 , EGFR was -5.33kJ mol -1 , and MTOR was -4.77 kJ mol -1 ,JAK2 was -3.25 KJ mol -1 . AKT1 and EGFR was further identified as the core targets. Conclusion Present study show that AKT1 and EGFR may be the key targets of SIN acting on the PI3K-Akt signaling pathway, thereby inhibiting the progression of disease and improving RA. Keywords: Sinomenine; Rheumatoid Arthritis; bioinformatics; Disclosure of Interests None declared Funding This project was supported by grants from National Natural Science Foundation of China (No. 81703783 and 81503415); Identification of new biomarkers for Sinomenine treatment in Rheumatoid Arthritis based on bioinformatics analysis XL Shen 1 , 2L ,YQ L 1 , 2Y ,X Guo 1 , 2 ,LF Wang 1 , 2 ,JK Zhang 1 , 2 ,ZT Feng 1 , 2* 1. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei 443002, China 2. Medical College of China Three Gorges University, Yichang, Hubei 443002, China †These authors contributed equally to this work. *Authors to whom correspondence should be addressed: Correspondence: Zhitao Feng E-mail: zhitao.feng@ctgu.edu.cn (Zhitao Feng) Disclosure of Interests None declared